Gel for treatment of skin diseases and for disinfection of the skin

ABSTRACT

Gel for local treatment of skin diseases and for prophylaxis, characterised by containing more than 90% of a drying and/or protein coagulating, short-chained alcohol or alcohol mixture, primarily ethanol, and possibly adjuvants or additives and by containing a gelling agent, that possesses good skin-adhesive properties, that gives a matrix formation of alcohol or alcohol mixtures, that creates an evaporation-inhibiting effect, gives a prolonged effect, and forms a protective plaster when the gel has dried.

This application concerns a matrix-forming and skin-adhesive,anti-evaporant gel for local treatment of skin diseases, for bothprimary and secondary prophylactic treatment of wounds, and for skindisinfection or the like in both humans and animals. More precisely, theinvention relates to a gel characterized by containing lower alkanol ina concentration of more than 90% and by containing a gelling agent, suchas ethyl(hydroxyethyl)cellulose or another suitable gelling agent, andpossible additives, whereby the gel can be applied to the skinefficiently, easily, and without complications.

BACKGROUND

Infectious skin diseases, both microbial and parasitic, are widespread.Some examples of skin diseases are viral skin infections caused by, forexample, Herpes simplex virus or Varicellae Zoster virus, bacterial skininfections caused by, for example, Staphylococcus aureus, fungalinfections caused by, for example, Trichophyton rubrum, for eliminatingskin parasites, such as Sarcoptes scabiei var. hominis. The virusinfection, Herpes simplex, alone occurs with approximately 100 millionnew cases per year.

Herpes simplex is caused by Herpes simplex virus (HSV). This virusoccurs in two antigenically different types, type 1 and type 2. Herpeson the lips and around the mouth (Herpes labialis) is usually caused bytype 1; most incidences of Herpes on and around the genitals (Herpesgenitalis) are caused by type 2.

The first infection with HSV (primary infection) variessymptomatologically. Usually it occurs during childhood. At this firstinfection, HSV-DNA is incorporated into the cells. Intermittently, virusproliferation occurs, resulting in Herpes outbreaks from thisincorporated HSV-DNA (these outbreaks are called secondary infections).Most Herpes outbreaks in adults are secondary, where the infectionflares up due to reduced resistance, febrile diseases (e.g. Pneumonia),traumas, or the effects of cold, heat, or light.

The outbreak starts with flushing, swelling, itching, and pain in theinfected area followed by necrosis and a suppurative ulceration which isthe most troublesome symptom. A spontaneous healing of the wounds willoccur in approximately 10 to 14 days.

The outbreak of Herpes genitalis--mentioned above--is identical to thatof Herpes labialis except for the fact that Herpes genitalis is locatedon and around the genitals.

The number of therapeutics for, for example, HSV skin infections is verylimited, and the present antiviral chemotherapy has not convincinglybeen proved efficient. Furthermore, there exists a few products foradvancing the healing of established HSV-wounds and inhibition offurther outbreaks. However, none of these products have a convincingeffect.

Bacterial infections such as pimples, isolated or in connection withAcne vulgaris, are examples of other skin diseases for which adequatetreatments are not currently available. In Acne it is currently believedthat lipolysis of triglycerides by Propionibacterium acnes releasesfatty acids; it is thought that these fatty acids are capable ofeliciting an inflammatory process in the follicle wall, which may thenrupture. Discharge of the follicular content leads to perifollicularinflammation. Benzoyl peroxide, which is currently used for-treatingacne, has a mode of action dependent upon its broad-spectrumantimicrobial effect on both primary inflammation and on secondaryinfection. Current treatments based on benzoyl peroxide have inherentproblems, including lack of efficacy and adverse reactions such aserythema, burning and desquamation of the skin.

From the literature it is known to use alcohol as disinfectant against,for example, virus including HSV--see, for example, R. Tyler; Journal ofHospital Infection (8: 22-29; 1987). When using alcohols as normalliquids a poor and very brief effect is achieved due to the very rapidevaporation of the alcohols. Also the use of alcohols at concentrationsbelow 90% by weight gives inadequate results.

Furthermore, Moldenhauer, in Zbl. Bakr. Hyg., I Abt. Orig. B 179,544-554 (1984) compares surface disinfection properties of ethanol,isopropanol, formaldehyde and benzalkonium chloride by suspending virussuspension (including HSV, influenza, cocksackie-B and mumps) in thosecompounds or solutions. Alcohol concentrations above 90% were nottested. Furthermore in these two references alcohol is being used forsurface disinfection properties and not for treatment of infections andthe symptoms thereof.

In U.S. Pat. No. 5,145,663, a disinfectant, consisting of 65-75%isopropyl alcohol, 8-12% propylene glycol, and potential inertingredients or disinfectants or antiseptics, is mentioned. The patentdoes not mention gels.

In GB-A-2017491 a gel containing alcohol is used as a hand-wash forbacterial disinfection.

In the above references describing the use of alcohol, either as such oras a solvent for other active disinfectant agents, in surfacedisinfection of the skin, the alcohol will remain in contact with theskin for a relatively short period of time. The compositions, if theyare washing compositions when they may contain a thickener such assodium chloride, are generally rinsed off with water. Treatment withno-rinse compositions and alcohol wipes applies a relatively low amountof composition and the alcohol evaporates quickly. The alcohol is, inparticular, not in contact with the skin long enough for penetration tolayers below the stratum corneum (dermis and epidermis).

Ethanol has been used extensively in pharmaceutical compositions usedfor topical application to the skin. Compositions including a gellingagent have, likewise, been used for such application. However in none ofthese disclosures is the alcohol itself used as an agent for treatingskin diseases. The following references are relevant.

In U.S. Pat. No. 3,016,328 and in U.S. Pat. No. 4,590,214 a mixture of adialdehyde and an alcohol is mentioned. Without evaluating the effect,it can be established that none of these products include alcohol andgel-forming agents.

WO 93/00114 describes a method for reducing the duration ofHSV-infection by applying a mixture of an anaesthetic and asurface-active ingredient with suitable antiviral activity. It does notmention gelling agents.

U.S. Pat. No. 4,247,547 mentions the use of gels containing alcohols andthe dermatologically active tretinoin for treatment of acne. Tretinoinis an irritant and the compositions would be wholly unsuitable fortreatment of skin infected by HSV. Also the concentration of water inthe compositions is unclear.

In Chemical Abstracts 90:76564r (1979) an antiseptic paste is disclosedcontaining about 80% by weight ethanol, 13% water and a thickener.

U.S. Pat. No. 5,013,545 describes a gel consisting of 60-90% ethanol,0.5-30% water, and an active ingredient, such as an antihistamine. Thispatent does not mention activity on viral skin infections such asHerpes. Further, none of the worked examples teaches how to produce astable gel with more than 80% alcohol.

U.S. Pat. No. 5,098,717 describes a gel based on 60-90% ethanol and asactive ingredients an antihistamine and an antipruritic.

Carrier gels for pharmaceuticals based on ethanol and water aredescribed in the patent literature, see, for example, SE 466134. In U.S.Pat. No. 4,593,048 it is mentioned that the penetration into thecirculation by pharmaceuticals, dissolved in ethanol and appliedtopically, is accelerated when various adjuvants are used. Theformulation contains surface-active ingredients as penetration aids forpharmaceuticals for percutaneous systematic administration. Thecompositions are not used to treat skin disorders.

An article by B. Rodu and F. Lakeman ("In vitro virucidal activity bycomponent of a topical film-forming medication," J. Oral Pathology 17:324326; 1988) mentions in vitro trials of a preparation consisting ofapproximately 80% ethanol, 7% tannic acid, 2.5% salicylic acid, and 1%boron acid. The tests were intended to evaluate the in vitro propertiesof the product Zilactin, which contains those ingredients and a hydroxypropylcellulose gelling agent. The in vivo performance of the gelagainst HSV has, however been found to be limited.

A specific antiviral preparation for topical treatment of Herpes isZovir/Zovirax cream (Zovir is a registered trademark), which contains 5%aciclovir. The efficacy has not been convincingly proved in relation toHerpes simplex skin infections, and, moreover, reports that resistanceis beginning to develop have been published.

Acyclovir has been administered systemically for the treatment ofVaricellae Zoster virus. However reports have indicated that thetreatment limited the immune response with consequent failure to developresistance to the disease.

Surprisingly, it has now turned out that it is possible to produce aneffective gel for treating skin diseases and for controlling skinparasites without using anti-histamines, anaesthetics, anti-inflammatoryagents, and totally without using pharmaceuticals, including biocidesagainst skin parasites.

Ethyl hydroxy ethylcellulose (EHEC) is produced by a first swellingnative cellulose in alkali, then adding ethylene oxide to cellulosehydroxyl groups activated in the first step, then etherifying hydroxylgroups in the product by reacting them with ethyl chloride after alkalitreatment. In the ethylene oxide treatment step ethoxy units may beadded to the hydroxyl group on a pendant group derived from the earlierreaction of an ethylene oxide molecule with a cellulose-hydroxyl group.In the etherification step, hydroxyl groups of pendant groups and ofcellulose-hydroxyl group may be reacted. The polymer product thuscontains ethoxy 2-ethoxyethyleneoxy and ethoxypoly(ethyleneoxy) pendantgroups. The reactions can be controlled so as to provide EHEC productswith a variety of different degrees of substitution, and molarsubstitution (i.e. a measure of the average ethyleneoxy units peretherified group). These parameters, as well as the degree ofpolymerisation/molecular weight, affect the properties of the polymer insolution.

The performance of EHEC in aqueous systems, where it is used as athickener and dispersing agent, for instance in paints and cement basedmortar, has been studied (Tornquist, J, Farg och Lack Scandinavia, 31,291-295 (1985), Carlsson, A et al polymer, 27, 431-436 (1986)). We arenot aware that its use to thicken or gel non-aqueous alcohols has beenstudied.

SUMMARY OF THE INVENTION

A new gel-form pharmaceutical composition according to the inventioncomprises a liquid and a high molecular weight polymer gelling agentdissolved in the liquid, characterised in that the composition comprisesmore than 90% by weight of a lower alkanol based on the total weight ofthe composition and less than 10% by weight water based on the totalweight of the composition.

The composition optionally comprises one (or more) enhancing agent whichenhances the effect of the alcohol. Preferably the composition issubstantially free of antihistamines, anaesthetics, anti-inflammatories,irritants and any immunogenic compounds or compounds which disturb theimmune system. Consequently, in the invention, concentration andcrystallization of medicaments (which is a potential problem with priorart compositions in which alcohol is held as a solvent vehicle for suchactive compounds) will not occur when the solvent evaporates.Consequently, local overdosing resulting in irritative inconveniences istotally avoided.

The lower alkanol preferably contains up to 4, preferably up to 3 carbonatoms. It may be a glycol or polyol but is preferably a mono hydroxycompound. It can be a mixture of such compounds. Most preferably itincludes ethanol optionally in combination with other lower alkanols.

Thus, it has now surprisingly been found that a gel containing more than90% ethanol or other lower alkanol is very effective for local treatmentof, for example, skin infections and skin parasites.

When using suitable gelling agents it is possible to transform aconcentrated alcohol into a very suitable, effective, and stable gel.The invention is of particular value in the treatment of viralinfections whose systems involve skin eruptions, especially herpesinfections.

DETAILED DESCRIPTION OF THE INVENTION

Thus, the preparation of the invention consists of concentrated alcoholin such a form that it is usable as a topical preparation for immediateapplication to the infected area of the skin including mucous membranes.While ethanol in lower concentrations, for example in concentrations ofless than 60%, gives a distinct pain reaction, the use of theconcentrated alcohol, for example in concentrations of more than 90%according to the invention, is almost painless even when it is used inopen wounds. The preparation has a combined effect which is utilisedoptimally and over a prolonged period in the invention. Thus, aneffective combination of drying the edematous tissue, coagulatingproteins and killing the infectious agent, is achieved, and later, whenit has dried, the gelling agent acts as a plaster protecting againstinfection.

The gels of the invention create a matrix formation that prevents thealcohol from leaking out of the gel and flowing away from the site wherethe gel has been applied. At the same time the gel is gentle to the skinand easy to apply. It is possible, and preferred, for the composition tobe transparent, and for the dried film of polymer gelling agent,remaining after the composition has dried on the skin, to be transparentto allow the underlying skin to be visible throughout treatment.

When the gel has dried it forms a protective film over a wound such asan HSV outbreak. Separately, all these activities contribute to avoidsecondary bacterial infection. With the evaporation-limiting matrixformation the gel forms a barrier film on the surface between gel andair by means of which the evaporation of alcohol is drastically reduced.For a long time the alcohol in this way remains in contact with the skinby which means the ethanol has a possibility of diffusing into the skinand perform its effect in depth. Further, the plaster action of the gelprevents a rapid evaporation of the alcohol diffused into the tissueand, finally, after drying the plaster effect of the gel will offerprotection against reinfection of the affected area. Thus, when choosinga gelling agent or a mixture of gelling agents, which form matrix withthe ethanol and that form a film on the surface of the gel against theatmosphere, the extraordinary prolonged effect of the gel is achievedaccording to the invention.

The content of water is important to the effectiveness. The contentshould be less than 10%, preferably less than 5%, and optimally, in somecases, less than 1%. The amount of water should be below the equilibriumcontent of the composition under ambient conditions, that is undernormal storage conditions at 20-24° C. and at 50-100% relative humidity,as well as at such humidity levels at temperatures up to bodytemperature (eg 37° C.). Thus the composition as a whole should, ineffect be hygroscopic. The hygroscopicity is preferably due to theconcentration of alkanol being higher than the concentration of alkanolin the presence of humid air. The equilibrium concentration of water inethanol under these conditions is in the range 3 to 7% by weight of thesum of water and ethanol. The gelling agent may also contribute somehygroscopicity. If the content of water is too high the drying andantimicrobial effect and especially the antiviral effect is reducedwhich means that the effectiveness of the gel is reduced. Similarly, theconcentration of alkanol is crucial to the effect on external skinparasites. It seems that the high concentration of alkanol may allow thealkanol to penetrate to layers of skin below the stratum corneum.

One of or a combination of several gelling agents which are usuallysoluble in the alkanol can be used. The gelling agent is a polymer,which may be linear, branched or cross-linked and may benaturally-derived, a derivative of such polymers, or may be whollysynthetic. The molecular weight is usually high, for instance at least10⁴, preferably at least 5×10⁵, and up to several million, for instancemore than 10⁶. The polymer is preferably non-ionic in the composition.Suitable gelling agents include cellulose derivatives, especiallycellulose ethers, such as ethylcellulose, methylcellulose; hydroxyethylcellulose especially ethyl(hydroxyethyl)cellulose (EHEC), alkyl- andhydroxyalkyl cellulose, carboxy methyl cellulose, other polysaccharides,such as naturally derived polysaccharides and derivatives thereof,including modified carragenan; and synthetic polymers such aspolyethylene glycols, polyethylene oxides, polyvinyl pyrrolidones andpoly acrylic acid.

The cellulose derivatives which are useful in the invention usually havea high molecular weight, for instance more than 10⁶, although polymerswith molecular weight from 10⁵ upwards may be useful. The degree ofsubstitution/derivatisation of cellulose ether derivatives useful in theinvention is preferably relatively high, for instance higher than 1.0.

A particularly suitable cellulosic gelling agent for a highlyconcentrated ethanol is EHEC, ethyl(hydroxyethyl)cellulose, which is aderivative of cellulose with CA registration number 9004-58-4. EHEC is,as an example, sold under the trademark BERMOCOLL from Berol Kemi AB,such as BERMOCOLL OS. For example, an effectively gelling EHEC isachieved at degree of polymerisation of approximately 3,200, a degree ofsubstitution of approximately 1.7 for ethylene (DS-ethyl=1.7) and ofapproximately 1.5 for hydroxyethyl (MS-hydroxyethyl=1.5).Celluloseethers including EHEC are more precisely described inKirk-Othmer, "Encyclopedia of Chemical Technology," 5:143,1979(3.edition). See also "Faerg och Lack Scandinavia" 31:291-298;1985.

Acrylic acid polymerics are also particularly suitable as gelling agent.Acrylic acid polymerics are, as an example, sold under the trademarkCarbopol from BF Goodrich, such as Carbopol 940 and 941, Carbopol 940 NFand 941 NF, Carbopol 980 NF and 981 NF, or Carbopol 1342 and 1382. ThoseCarbopols are high molecular, non-linear polymerics of acrylic acidcross-linked with polyalkenyl polyether. Acrylic acid polymerics aremore precisely described in "Kirk-Othmer, Encyclopedia of Chem.Tech,"20:216;1982 and in Ullmanns Encyclopedia of Ind.Chem," A21:752;1992.

Polyvinylpyrrolidones are a third example of a particularly suitablegelling agent. Polyvinylpyrrolidones, as an example, are sold under thetrademark PVP K-30 and PVP K-90 from GAF. Polyvinylpyrrolidones are highmolecular polymerics which are described in more detail in "Kirk-Otmer,Encyclopedia of Chem.Tech.," 23:963;1983 and in "Ullmanns Encyclopediaof Ind.Chem.," A21:143;1992 and others.

The gelling agents are used in amounts between 0.1% and 10%, dependingon the choice of gelling agent or mixture of gelling agents, dependingon the composition, the desired texture etc. The amount shouldpreferably be sufficient to render the composition gel-like at roomtemperature and at normal body temperature so that it remains in placeon the skin and does not spread or run of f after application. Thegel-like consistency, which is due to the viscoelastic properties ofpolymer solutions in solvents, depends upon molecular weight, degree ofsubstitution as well as, for derivatives such as EHEC where the severalunits of derivatising agent may be added to each derivatised saccharidehydroxyl group, the molar substitution and type of substituent as wellas the concentrations of polymer in the composition. The compositionsshould generally have high viscosity under low shear but, for optimalhandling during manufacture and application, should be shear thinning.This combination of features can be achieved by appropriate selection ofproperties, as illustrated in the accompanying examples, for instance.For example, the viscosity-increasing effect of EHEC depends on thedegree of polymerization and on the degree of substitution and, for theEHEC having a degree of polymerisation of 3200, mentioned above, asuitable concentration in ethanol is 0.5 to 2.0%, for instance around1.0%.

This, for example, applies to pH-regulating agents such as bases, egalkaline inorganic compounds or organic bases and mixtures by which theaction of the alcohol is increased under certain circumstances.Inorganic bases which may be used include sodium and potassium hydroxideand carbamate. Organic bases include triethylamine, triethanol amine andother alkanolamines. For example, a content of 0.02% NaOH will increasethe antiviral action of the ethanol. Thus in one embodiment of theinvention the composition has a pH in the range 6 to 9.5, preferably analkaline pH. Other additives that can be mentioned are the substancesthat form part of medicinal gels such as emollients, colorants,perfumes, menthol, camphor, W-protective agents etc. and the like bywhich the gel can be supplemented with further functional properties.

The composition should, however, be substantially free ofpharmacologically active ingredients other than these optional enhancingagents.

The composition is preferably supplied in an air and moisture/moisturevapour-impermeable container. Such containers are, for instance,squeezable tubes, especially formed of metal foils or of plasticsmaterials having moisture barrier properties. Such containers preventcompositions, whose water content is such that the composition ishygroscopic, from absorbing moisture from the atmosphere during storageand before use. By the use of such containers, therefore loss of dryingactivity of the gels is minimised.

According to the invention we have not only succeeded in producing agel--with a concentrated content of alkanol--which is very effective andsuitable for treatment of skin diseases, which is skin-adhesive andgentle to the skin, and which preferably does not contain othermedicaments or pharmaceuticals. The mere omission of medicaments andpharmaceuticals such as antihistamines etc. has as a consequence that noreverse actions or side-effects occur and that allergic reactions arecompletely eliminated. Further to this, as a consequence of the specialmechanism of activity of ethanol, absolutely no resistance can developamong the responsible microorganisms or parasites. In choosing a gelwith a matrix structure it is achieved that the ethanol, afterapplication, does not accumulate in, for example, the nasolabial fissureat the angle of the mouth or in the groin but remains where applied.Further, as the gel shows pseudoplastic (viscoelastic) properties thegel is very easy to apply, and at the same time it regains its matrixstructure and its structural firmness and exactly by that, as mentioned,remains on the site of application.

Because of the high concentration of alcohol the gel possesses othersurprising properties. The skin-adhesive properties turn out to be verygood, partially due to, the high content of alkanol, but also because ofthe choice of gelling agent, where especially EHEC, ASP, and PVP orcombinations of these have lipophilic and hydrophilic properties givingthe alcohol a very good contact with the skin.

The gelling agents, especially EHEC, ASP, and PVP or combinations ofthese, have hydrophobic-hydrophilic properties by which the release ofalcohol towards the skin from the slow release matrix structure of thegel is adjustable. By doing this, it can be obtained that norelease-inhibiting film is created between the alcohol-gel and theskin/mucous membranes. This, of course, is important for the continuouseffect of the alcohol-gel on the site of application.

Thus, it is not necessary to add surfactants to achieve the correctcontact between the skin and the gel as is the case in U.S. Pat. No.4,593,048. The composition should generally be free of addedsurfactants.

Similarly, it is not necessary to add special binding agents nor to useplaster or tape in order to adhere the gel to the skin.

Gels according to the invention are physically and chemically stable forat least 12 months at 50° C. Among other things this is a result of thefact that addition of other active ingredients or adjuvants, whichtogether with medicament or biocide may be labile during production andstorage, is not needed. It is not necessary to add actual medicamentsthat, in turn, would require protective antioxidants etc. to secure thechemical stability of the very same medicaments during production andstorage.

As the gel does not contain actual skin irritants it is, as mentioned,not necessary to add anti-irritants such as anti-histamines,anti-inflammatory agents or similar agents.

Because of the concentrated content of alcohol the gel isself-preserving. It is therefore not necessary to add antimicrobialpreservatives against fungoid growths nor products against bacteria orother micro-organisms, and it is not necessary to store the gel inrefrigerator or the like. Omitting all these additives in the gel meansthat undesirable side-effects of such additives are eliminated.

Two very important properties are achieved in the invention by omittingsurfactants, skin adhesives, pharmaceuticals, medicaments, antioxidants,antihistamines, or other anti-inflammatory agents, and because it is notnecessary to add preservatives against fungi, bacteria, or othermicro-organisms to the gel. First, in all simplicity, the gel iscomposed of non-allergenic substances. Secondly, owing to its specialmode of action towards the infectious agents ethanol does not give riseto development of resistance. Furthermore the product does not disturbthe hosts immune response.

For the sake of completeness it should be mentioned that many skindiseases, for example, Herpes simplex are complicated by secondary,usually bacterial infections. It is not necessary to add otherpharmaceuticals to the gel to avoid secondary infections, as the alcoholin the gel with the long-term effect disinfects the area and protects itagainst reinfection via the plaster effect of the dried gel until thewound has healed.

Especially regarding Herpes infections the drying and proteincoagulating effect is of great importance. During the primary phase ofthe repeated herpes outbreaks (secondary infections) are characterizedby the formation of blisters, full of liquid. Apart from an immediateimprovement of the itching and the pain reaction, a drying action on theblisters, that have already formed, is achieved when the preparation isapplied at an early stage, and thus the blisters will disappear rapidly.If the herpes outbreak is not treated early enough the blisters willburst resulting in the formation of suppurating, open wounds that arecharacteristic of the secondary phase. When used during this phase, thepreparation has an immediate drying effect by means of which thesecretion ends, and the protein coagulating action destroy thesuperficial, necrotic cells. The drying effect makes the product usefulon moist skin areas. Here the drying effect has an immediateprophylactic action in relation to bacterial infections through areduction of the growth conditions.

Similar advantages are seen when the gel is used to treat skin eruptionsassociated with other viral infections such as chickenpox. When appliedto such skin eruptions the formation of blisters is prevented or theyare dried and itching is minimised. The breaking of the skin withsubsequent risk of infection is thus prevented.

In this connection we can also mention accidental skin injuries such aswounds and skin abrasions where the antimicrobial effect combined withthe plaster action of the gel after drying has an indisputablepreventive action in relation to wound infections.

The gel is further suitable for prophylactic treatment of physical skininjuries such as cuts, abrasions etc. This indication is not only basedon the antimicrobial property of the preparation, but also on theprotective effect of the dried gel having the "built-in" plaster effectthat is achieved when the preparation has dried.

It is believed that use of the preparation in connection with treatmentof burns will have a useful infectious prophylactic effect. Someeczematous diseases including allergic skin diseases are characterizedby secondary infections. Here the invention will have great importancetoo, not least because of the non-allergenic property of thecomposition.

As mentioned above the gel is suitable for controlling externallyparasitical and troublesome organisms. For example, the gel is suitablefor external treatment of scabies, chigger and other ectoparasites.

A very effective preparation against skin infections and for eliminatingexternal skin parasites can be obtained when using a gel in which theliquid consists of concentrated ethanol or a concentrated mixture ofethanol and other short-chained alcohols such as isopropanol orpropylene glycol and containing in addition, additives such as dryingand disinfecting agents, as well as the gelling agent, but no otheringredients.

The gel is also found to be useful for application to the site of insetbites and stings. The effect is thought to be due at least partially tothe function of the concentrated alcohol in causing toxoid proteins inthe sting to coagulate and be rendered inactive.

The invention is further illustrated in the following examples.

EXAMPLES

Examples of compositions of the gel:

Example 1

    ______________________________________                                        Ingredient      Weight in %                                                   ______________________________________                                        Ethanol 99.9%   91                                                              Water                   7                                                     Carbopol 980 NF         2                                                   ______________________________________                                    

Carbopol 980 NF (trade mark, BF Goodrich) has a molecular weight ofaround 7.5×10⁵.

Example 2

    ______________________________________                                        Ingredient      Weight in %                                                   ______________________________________                                           Ethanol 999% 95                                                              Water                  3                                                      carbopol 980 NF        2                                                      Perfume  --                                                                 ______________________________________                                    

Example 3

    ______________________________________                                        Ingredient       Weight in %                                                  ______________________________________                                        Ethanol 99.9%   min. 99                                                         Carbopol 940 NF*   max.                                                     ______________________________________                                            *Carbopol 940 NF (registered trademark) an acrylic acid   polymer from     BF Goodrich                                                              

Example 4

    ______________________________________                                        Ingredient       Weight in %                                                  ______________________________________                                        Ethanol 99.9%    97.3                                                           Bermocoll OS*                      2.3                                        NaOH or triethylamine             0.1                                         Water                              0.3                                      ______________________________________                                         *Bermocoll OS (registered trademark) from BerolNobel =                        Ethyl(hydroxyethyl)cellulose                                             

Example 5

    ______________________________________                                        Ingredient     Weight in %                                                    ______________________________________                                        Ethanol 99.9%  91.0                                                             EHEC*                        1.5                                              Glycerine                    1.0                                              Propyleneglycol              3.0                                              Water                        3.5                                            ______________________________________                                         (DP       =  1,600, DSethyl = 0.8, MShydroxyethyl =  2.0)                

Example 6

    ______________________________________                                          Ingredient       Weight in %                                                ______________________________________                                        Ethanol 99.9%      91.0                                                         PVP K-30*                    2.5                                              UV-absorbent                 1.0                                              Camphor                      0-0.5                                            Propylene glycol or adjuvant 0-3.0                                            Water                        0-2.0                                            Polyvinyl alcohol            0-1.0                                          ______________________________________                                          *PVP K30 (registered trademark) from GAF   = Polyvinylpyrrolidone,           average molecular weight of 4 × 10.sup.4.                          

Example 7

    ______________________________________                                        Ingredient     Weight in %                                                    ______________________________________                                        Ethanol        91                                                               Carbopol 940         1                                                        PVP K-90            2                                                         Water               4                                                         Surfactant          2                                                       ______________________________________                                    

Example 8

    ______________________________________                                        Ingredient       Weight in %                                                  ______________________________________                                        Ethanol          91.0                                                           Hydroxypropylcellulose                 2.5                                    Xanthan gum                            0.1                                    Isopropanol                            4.0                                    Water                                  2.4                                  ______________________________________                                    

The hydroxypropyl cellulose is selected for its solubility in theliquid.

Example 9

    ______________________________________                                        Ingredient       Weight in %                                                  ______________________________________                                        Ethanol          93.0                                                           Hydroxyethylcellulose                  1.0                                    Ethylcellulose                         0.5                                    Methylcellulose                       0.5                                     NaOH                                   0.02                                   Water                                  4.98                                 ______________________________________                                    

All the cellulose derivatives are selected for their solubility in theliquid.

Example 10

    ______________________________________                                         Ingredient            Weight in %                                            ______________________________________                                        Ethanol                95.0                                                     Ethylhydroxyethylcellulose (Bermocoll OS)     1.0                             Polyvinylpyrrilidone (MW 3.5 × 10.sup.4)           2.2                  Polyethyleneglycol (MW 2 × 10.sup.3)               0.2                  KOH                                           0.02                            Water                                         1.58                          ______________________________________                                    

Examples of the use of the gels:

Example 11

Local treatment of Herpes simplex

When used for local treatment of Herpes simplex the effect depends onthe time of application in relation to the start of the infection. Gelswith particularly high concentration of alcohol are suitable, forexample, gels mentioned in example 3, 4 or 10.

Within the first hours of the first phase which is characterized byitching, slight pain and prickling, followed by formation of vesicles,the gel is applied to the affected area approximately once an hour. Thesubjective symptoms dwindle immediately, and after 3-5 applications theoutbreak is stopped and the vesicles disappear. After this, the gel isre-applied every 3-5 hours for 24 hours to secure that the outbreak hasstopped completely.

When treatment is not started before the vesicles have burst and the gelis applied with a frequency of about every 3 hours the wounds are keptdry without the suppuration. The treatment is continued with decreasingapplication frequency until all wounds have started healing.

All three gels gave good results when used at these stages of theinfection.

Example 12

Treatment of Herpes zoster

When used for treating local skin outbreaks of Herpes zoster the gelmentioned in example 2 and 9 have been applied to the affected area.During the first 24 hours the gel is applied approximately every 2hours, and after that at longer intervals as required. The vesicles healup and the patient's inconveniences will abate rapidly.

Example 13

Treatment of bacterial skin infections

The treatment of skin infections in connection with Acne vulgaris shouldbe mentioned as an example of treating bacterial skin infections.

Gel in accordance with examples 1 and 6 according to the invention isapplied to the infected skin areas. To begin with the gel is applied 3times a day, and after that, when the infected areas have dried it isapplied approximately once or twice a day. By means of this treatmentwith each of the gels rapid healing is achieved. A gel, in accordancewith example 3, can be used in difficult cases directly on extensivelyinfected areas.

Example 14

Treatment of mycologic skin infections

The treatment of epidermophytosis (Tinea pedis) should be mentioned asan example of treating mycologically conditioned infections. Rapidhealing of fissures, and successive cure of the fungus infection isachieved when a gel, in accordance with example 4, 7 and 8, is appliedtwice a day primarily, and after a few days only once a day.

Example 15

Control of external parasites

As required a thin or thick layer of a gel, in accordance with example 3and 9 of the invention, is applied to the infected area with theexternal parasites such as lice, scab mites, ticks and crab lice. In ashort time the parasites are eliminated.

Because of the antimicrobial property of the gel, secondary infectionsafter bites also heal up rapidly.

Example 16

Prophylacticum against skin infections

The treatment of banal scraping wounds should be mentioned as an exampleof using the gel as a prophylacticum. Primarily the wound is cleansedwith water/soap following classic principles. After that, gel isapplied, for example, the gel mentioned in example 1. During the first24 hours the gel is applied 3 times. After that, the gel is applied oncea day until the wounds start to heal. Due to the properties of the driedgel, acting as an elastic, fixed plaster on the wound, a good protectionof the wounds is achieved in between the applications.

Example 17

Treatment of Chicken pox (Variola)

The gel of example 4 is applied directly onto the individual eruptionson the skin of a patient with chickenpox as soon as possible after theeruption and every 2 to 4 hours thereafter. This immediately soothes theskin, reduces itching, prevents blister formation and renders thepatient non-contagious in a shorter period of time. The gels of examples3 and 10 have similar activity.

Example 18

Bee Sting and Other Insect Bite Treatment

The gel of example 4 is applied direct to the skin at the site of a beesting as soon as possible after occurrence of the sting. The discomfortand swelling were immediately reduced and itching does not develop. Thisactivity is thought to be due to an effect of the concentrated alcoholin coagulating protein in the insect venom injected into the skin. Thegels of examples 3 and have similar performance.

We claim:
 1. A gel form pharmaceutical composition for the treatment ofskin disorders comprising a liquid and a polymer gelling agent dissolvedin the liquid, wherein the composition comprises more than 90% by weightof at least one C₁₋₄ alkanol based on the total weight of thecomposition and less than 10% by weight water based on the total weightof the composition, wherein said polymer gelling agent has a molecularweight of at least 10,000, wherein said alkanol is substantially theonly active agent in said composition and said composition is free ofany additional ingredients which would substantially reduce gelstability.
 2. A composition according to claim 1 in which theconcentration of water in the composition is less than the equilibriumcontent at temperatures in the range 20-24° C. and 50 to 100% relativehumidity.
 3. A composition according to claim 1 consisting essentiallyof the gelling agent, alkanol and water.
 4. A composition according toclaim 1, wherein said composition further consists essentially of aneffective amount of an enhancing agent which enhances the effect of thealkanol in the treatment of said skin disorder.
 5. A compositionaccording to claim 4 wherein the enhancing agent consists of a base. 6.A composition according to claim 1 in which the alkanol is selected fromethanol, isopropanol or mixtures thereof.
 7. A composition according toclaim 1 in which the gelling agent is a derivative of cellulose.
 8. Acomposition according to claim 1 in which the concentration of water isless than 5% based on the weight of alkanol plus water.
 9. A compositionaccording to claim 1 contained in a moisture- and moisturevapour-impervious container.
 10. A method for the treatment of skininfected by a virus comprising administering a polymer gelling agent andmore than 90% by weight of at least one C₁₋₄ alkanol and less than 10%water, based on the total composition weight to a patient in need ofsaid treatment, wherein said alkanol is substantially the only activeagent in said composition and said composition is free of any additionalingredients which would substantially reduce gel stability.
 11. Themethod according to claim 10 in which the viral infection is of Herpessimplex virus.
 12. A method for the treatment of skin havingectoparasites comprising applying to the skin of a patient in need ofsuch treatment a composition comprising a polymer gelling agent and morethan 90% by weight of at least one C₁₋₄ alkanol and less than 5% byweight of water, based on the total composition, wherein said alkanol issubstantially the only active agent in said composition.
 13. A method oftreatment of infected skin by topical application to the infected areaof skin of a gel form pharmaceutical composition comprising a polymergelling agent, more than 90% by weight of at least one C₁₋₄ alkanol,based on the weight of the total composition and less than 10% by weightwater based on the total weight of composition, wherein said alkanol issubstantially the only active agent in said composition and saidcomposition is free of any additional ingredients which wouldsubstantially reduce gel stability.
 14. A method according to claim 13in which the treatment is effective to affect a layer of skin deeperthan the stratum corneum.
 15. A method according to claim 13 in whichthe composition remains in contact with the area affected by theinfection for a period of at least 2 hours, to form a cohesive barrierfilm of said polymer.
 16. A method of treatment of disorders of layersof the skin below the stratum corneum by topical application to the skinof a composition as recited in claim
 1. 17. A composition according toclaim 5 wherein said base is an inorganic alkali.
 18. A compositionaccording to claim 17 wherein said inorganic alkali is sodium hydroxideor potassium hydroxide.
 19. A composition according to claim 5 whereinsaid base is an organic base.
 20. A composition according to claim 19wherein said organic base is triethylamine.
 21. A composition accordingto claim 6 in which the alkanol is ethanol.
 22. A composition accordingto claim 7, in which the derivative of cellulose is a cellulose ether.23. A composition according to claim 7 in which the derivative ofcellulose is ethyl hydroxyethyl cellulose.
 24. A composition accordingto claim 5, wherein the enhancing agent is added in an amount such thatthe composition has a pH in the range from 6 to 9.5.
 25. A compositionaccording to claim 18, wherein sodium hydroxide or potassium hydroxideis added in an amount such that the composition has a pH in the rangefrom 6 to 9.5.
 26. A composition according to claim 20, whereintriethylamine is added in an amount such that the composition has a pHin the range from 6 to 9.5.
 27. A composition according to claim 1,consisting of gelling agent, liquid consisting of C₁₋₄ alkanol andwater, and optional additives selected from the group consisting of pHregulating agents, emollients, colorants, perfumes, menthol, camphor,and UV protective agents.
 28. A composition according to claim 1, whichis substantially free of antihistamines, anesthetics andanti-inflammatories.
 29. A composition according to claim 24, whereinthe amount of water in the composition is below the equilibrium contentof water in the composition at 20 to 37° C. and at 50 to 100% relativehumidity.
 30. A composition according to claim 1, wherein the alkanol isa C₃₋₄ -alkanol.
 31. A composition according to claim 1, wherein thealkanol is a C₃ -alkanol.
 32. A method according to claim 12, whereinsaid ectoparasites cause scabies.